Polyetheretherketone(PEEK)has been recognized for its immense potential in hard tissue repair applications due to its mechanical properties resembling those of natural bones.However,the inherent bioinertness of pristi...Polyetheretherketone(PEEK)has been recognized for its immense potential in hard tissue repair applications due to its mechanical properties resembling those of natural bones.However,the inherent bioinertness of pristine PEEK results in insufficient osseointegration.Moreover,implant-associated infection(IAI)has become a serious threat in orthopedic surgery.These risks usually lead to implant loosening,delayed healing,and even the failure of implantation,hampering many clinical applications of PEEK.In this study,we present a facile strategy to endow PEEK implants with enhanced osseointegration and pH-responsive antibacterial activity.Briefly,pristine PEEK was first treated with mixed acids to obtain a porous structure(referred to as SNPEEK),and then the metal-phenolic networks(MPN)coating was prepared using layer-by-layer(LbL)assembly consisting of Sr^(2+) and tannin acid(TA)(referred to as ST coating).The results demonstrated that the dual-functional PEEK displayed enhanced antibacterial activity in pH-responsive manner.At pH 7.4,the antibacterial ratios were 71.72%and 66.79%against Staphylococcus aureus(MSSA,ATCC 25,923)and methicillin-resistant Staphylococcus aureus(MRSA,ATCC BAA-40),respectively.Remarkably,at pH 5.5,the antibacterial activities significantly increased,resulting in killing ratios of 99.98%and 100%,respectively.Furthermore,the dual-functional PEEK promoted osteogenic differentiation of pre-osteoblasts(MC3T3-E1)and migration of human umbilical vascular endothelial cells(HUVECs).In addition,the dual-functional PEEK demonstrated effective anti-infection ability and desirable new bone formation ability in vivo compared to both pristine PEEK and SNPEEK implants.Overall,this study provides a promising strategy to endow PEEK implants with effective osseointegration and anti-infective ability,representing a prospective solution to address current clinical challenges associated with PEEK implants.展开更多
The circadian clock participates in maintaining homeostasis in peripheral tissues,including intervertebral discs(IVDs).Abnormal mechanical loading is a known risk factor for intervertebral disc degeneration(IDD).Based...The circadian clock participates in maintaining homeostasis in peripheral tissues,including intervertebral discs(IVDs).Abnormal mechanical loading is a known risk factor for intervertebral disc degeneration(IDD).Based on the rhythmic daily loading pattern of rest and activity,we hypothesized that abnormal mechanical loading could dampen the IVD clock,contributing to IDD.Here,we investigated the effects of abnormal loading on the IVD clock and aimed to inhibit compression-induced IDD by targeting the core clock molecule brain and muscle Arnt-like protein-1(BMAL1).In this study,we showed that BMAL1 KO mice exhibit radiographic features similar to those of human IDD and that BMAL1 expression was negatively correlated with IDD severity by systematic analysis based on 149 human IVD samples.The intrinsic circadian clock in the IVD was dampened by excessive loading,and BMAL1 overexpression by lentivirus attenuated compression-induced IDD.Inhibition of the RhoA/ROCK pathway by Y-27632 or melatonin attenuated the compression-induced decrease in BMAL1 expression.Finally,the two drugs partially restored BMAL1 expression and alleviated IDD in a diurnal compression model.Our results first show that excessive loading dampens the circadian clock of nucleus pulposus tissues via the RhoA/ROCK pathway,the inhibition of which potentially protects against compression-induced IDD by preserving BMAL1 expression.These findings underline the importance of the circadian clock for IVD homeostasis and provide a potentially effective therapeutic strategy for IDD.展开更多
Low back pain is one of the most serious public health problems worldwide and the major clinical manifestation of intervertebral disc degeneration(IVDD).The key pathological change during IVDD is dysfunction of the an...Low back pain is one of the most serious public health problems worldwide and the major clinical manifestation of intervertebral disc degeneration(IVDD).The key pathological change during IVDD is dysfunction of the annulus fibrosus(AF).However,due to the lack of an in-depth understanding of AF biology,the methods to reconstruct the AF are very limited.In this study,the mice AF cell atlas were decoded by single-cell RNA sequencing to provide a guide for AF reconstruction.The results first identify a new population of AF cells,fibrochondrocyte-like AF cells,which synthesize both collagen Ⅰ and collagen Ⅱ and are potential functional cells for AF reconstruction.According to the dual features of the AF extracellular matrix,a composite hydrogel based on the acylation of methacrylated silk fibroin with methacrylated hyaluronic acid was produced.To obtain the ability to stimulate differentiation,the composite hydrogels were combined with a fibrochondrocyte-inducing supplement.Finally,reconstruction of the AF defects,by the novel AF stem cell-loaded composite hydrogel,could be observed,its amount of chondroid matrices recovered to 31.7% of AF aera which is significantly higher than that in other control groups.In summary,this study decodes the AF cell atlas,based on which a novel strategy for AF reconstruction is proposed.展开更多
The emergence of human coronaviruses(HCoVs),especially the current pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),engender severe threats to public health globally.Despite the outstandi...The emergence of human coronaviruses(HCoVs),especially the current pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),engender severe threats to public health globally.Despite the outstanding breakthrough of new vaccines and therapeutic medicines in the past years,HCoVs still undergo unpredictable mutations,thus demanding more effective diagnostic and therapeutic strategies.Benefitting from the unique physicochemical properties and multiple nano-bio interactions,nanomaterials hold promising potential to fight against various HCoVs,either by providing sensitive and economic nanosensors for rapid viral detection,or by developing translatable nanovaccines and broad-spectrum nanomedicines for HCoV treatment.Herein,we systemically summarized the recent applications of nanoagents in diagnostics and therapeutics for HCoV-induced diseases,as well as their limitations and perspectives against HCoV variants.We believe this review will promote the design of innovative theranostic nanoagents for the current and future HCoV-caused pandemics.展开更多
基金supported by the National Natu-ral Science Foundation of China(No.52073230)the Shaanxi Provincial Science Fund for Distinguished Young Scholars(No.2023-JC-JQ-32).
文摘Polyetheretherketone(PEEK)has been recognized for its immense potential in hard tissue repair applications due to its mechanical properties resembling those of natural bones.However,the inherent bioinertness of pristine PEEK results in insufficient osseointegration.Moreover,implant-associated infection(IAI)has become a serious threat in orthopedic surgery.These risks usually lead to implant loosening,delayed healing,and even the failure of implantation,hampering many clinical applications of PEEK.In this study,we present a facile strategy to endow PEEK implants with enhanced osseointegration and pH-responsive antibacterial activity.Briefly,pristine PEEK was first treated with mixed acids to obtain a porous structure(referred to as SNPEEK),and then the metal-phenolic networks(MPN)coating was prepared using layer-by-layer(LbL)assembly consisting of Sr^(2+) and tannin acid(TA)(referred to as ST coating).The results demonstrated that the dual-functional PEEK displayed enhanced antibacterial activity in pH-responsive manner.At pH 7.4,the antibacterial ratios were 71.72%and 66.79%against Staphylococcus aureus(MSSA,ATCC 25,923)and methicillin-resistant Staphylococcus aureus(MRSA,ATCC BAA-40),respectively.Remarkably,at pH 5.5,the antibacterial activities significantly increased,resulting in killing ratios of 99.98%and 100%,respectively.Furthermore,the dual-functional PEEK promoted osteogenic differentiation of pre-osteoblasts(MC3T3-E1)and migration of human umbilical vascular endothelial cells(HUVECs).In addition,the dual-functional PEEK demonstrated effective anti-infection ability and desirable new bone formation ability in vivo compared to both pristine PEEK and SNPEEK implants.Overall,this study provides a promising strategy to endow PEEK implants with effective osseointegration and anti-infective ability,representing a prospective solution to address current clinical challenges associated with PEEK implants.
基金the National Natural Science Foundation of China(82020108019,82130070,81730065,82002347,81972032,and 81902202)The Medical Research Council(UK)MR/T016744/1 and MR/P010709/1the Versus Arthritis Senior Research Fellowship Award 20875.
文摘The circadian clock participates in maintaining homeostasis in peripheral tissues,including intervertebral discs(IVDs).Abnormal mechanical loading is a known risk factor for intervertebral disc degeneration(IDD).Based on the rhythmic daily loading pattern of rest and activity,we hypothesized that abnormal mechanical loading could dampen the IVD clock,contributing to IDD.Here,we investigated the effects of abnormal loading on the IVD clock and aimed to inhibit compression-induced IDD by targeting the core clock molecule brain and muscle Arnt-like protein-1(BMAL1).In this study,we showed that BMAL1 KO mice exhibit radiographic features similar to those of human IDD and that BMAL1 expression was negatively correlated with IDD severity by systematic analysis based on 149 human IVD samples.The intrinsic circadian clock in the IVD was dampened by excessive loading,and BMAL1 overexpression by lentivirus attenuated compression-induced IDD.Inhibition of the RhoA/ROCK pathway by Y-27632 or melatonin attenuated the compression-induced decrease in BMAL1 expression.Finally,the two drugs partially restored BMAL1 expression and alleviated IDD in a diurnal compression model.Our results first show that excessive loading dampens the circadian clock of nucleus pulposus tissues via the RhoA/ROCK pathway,the inhibition of which potentially protects against compression-induced IDD by preserving BMAL1 expression.These findings underline the importance of the circadian clock for IVD homeostasis and provide a potentially effective therapeutic strategy for IDD.
基金the financial support of the following funds for our study:The State Key Program of National Natural Science Foundation of China(Grant nos.81730065 to Z.L.,82130070 to L.Y.)Projects of International Cooperation and Exchanges of National Natural Science Foundation of China(Grant nos.82020108019 to Z.L.).
文摘Low back pain is one of the most serious public health problems worldwide and the major clinical manifestation of intervertebral disc degeneration(IVDD).The key pathological change during IVDD is dysfunction of the annulus fibrosus(AF).However,due to the lack of an in-depth understanding of AF biology,the methods to reconstruct the AF are very limited.In this study,the mice AF cell atlas were decoded by single-cell RNA sequencing to provide a guide for AF reconstruction.The results first identify a new population of AF cells,fibrochondrocyte-like AF cells,which synthesize both collagen Ⅰ and collagen Ⅱ and are potential functional cells for AF reconstruction.According to the dual features of the AF extracellular matrix,a composite hydrogel based on the acylation of methacrylated silk fibroin with methacrylated hyaluronic acid was produced.To obtain the ability to stimulate differentiation,the composite hydrogels were combined with a fibrochondrocyte-inducing supplement.Finally,reconstruction of the AF defects,by the novel AF stem cell-loaded composite hydrogel,could be observed,its amount of chondroid matrices recovered to 31.7% of AF aera which is significantly higher than that in other control groups.In summary,this study decodes the AF cell atlas,based on which a novel strategy for AF reconstruction is proposed.
基金This work was supported by the National Natural Science Foundation of China(Nos.52003222 and 21875189)Ningbo Natural Science Foundation(No.202003N4064)+2 种基金Natural Science Foundation of Chongqing(No.cstc2020jcyj-msxmX0752)the Joint Research Funds of Department of Science&Technology of Shaanxi Province and Northwestern Polytechnical University(No.2020GXLH-Z-013)the Fundamental Research Funds for the Central Universities.The TOC,Figs.1 and 2 in this review were created with BioRender.com.
文摘The emergence of human coronaviruses(HCoVs),especially the current pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),engender severe threats to public health globally.Despite the outstanding breakthrough of new vaccines and therapeutic medicines in the past years,HCoVs still undergo unpredictable mutations,thus demanding more effective diagnostic and therapeutic strategies.Benefitting from the unique physicochemical properties and multiple nano-bio interactions,nanomaterials hold promising potential to fight against various HCoVs,either by providing sensitive and economic nanosensors for rapid viral detection,or by developing translatable nanovaccines and broad-spectrum nanomedicines for HCoV treatment.Herein,we systemically summarized the recent applications of nanoagents in diagnostics and therapeutics for HCoV-induced diseases,as well as their limitations and perspectives against HCoV variants.We believe this review will promote the design of innovative theranostic nanoagents for the current and future HCoV-caused pandemics.
